1. 6 Energy, Enzymes, and Metabolism

2. 6 Energy and Energy Conversions To physicists, energy represents the capacity to do work. To biochemists, energy represents the capacity for change. Cells must acquire energy from their environment. Cells cannot make energy; energy is neither created nor destroyed, but energy can be transformed.

3. 6 Energy and Energy Conversions There are two main types of energy:  Potential energy is stored energy.  Kinetic energy is energy of motion.

4. 6 Energy and Energy Conversions Metabolism can be divided into two types of activities:  Anabolic reactions link simple molecules together to make complex ones. These are energy-storing reactions.  Catabolic reactions break down complex molecules into simpler ones. Some of these reactions provide the energy for anabolic reactions.

5. 6 Laws of Thermodynamics  First Law: Energy cannot be created nor destroyed  However, it can be transformed from one type to another, such as photoenergy to chemical energy  Second Law: Not all energy in a system can be used and disorder of the system will spontaneously increase (termed entropy)  Local entropy can be overcome by applying energy  Living organisms use energy to build order from disorder

6. 6 Energy and Energy Conversions In any system: total energy = usable energy + unusable energy Or: enthalpy (H) = free energy (G) + entropy (S) H = G + TS (T = absolute temperature) Entropy is a measure of the disorder of a system. Usable energy: G = H – TS

7. 6 Energy and Energy Conversions Change in each at a constant temperature can be measured precisely in calories or joules.  G =  H – T  S If  G is positive (+), free energy is required. This is the case for anabolic reactions. If  G is negative (–), free energy is released. This is the case for catabolic reactions.

8. 6 Energy and Energy Conversions If a chemical reaction increases entropy, its products are more disordered or random than its reactants are. An example is the hydrolysis of a protein to its amino acids. Free energy is released,  G is negative, and  S is positive (entropy increases). When proteins are made from amino acids, free energy is required, there are fewer products, and  S is negative.

9. 6 Energy and Energy Conversions Anabolic reactions may make single products from many smaller units; such reactions consume energy (+  G). Catabolic reactions may reduce an organized substance (glucose) into smaller, more randomly distributed substances (CO 2 and H 2 O). Such reactions release energy (–  G).

10. 6 Energy and Energy Conversions A spontaneous reaction goes more than halfway to completion without input of energy, whereas a nonspontaneous reaction proceeds that far only with an input of energy. Spontaneous reactions are called exergonic and have negative  G values (they release energy). Nonspontaneous reactions are called endergonic and have positive  G values (they consume energy).

11. Figure 6.3 Exergonic and Endergonic Reactions (- ∆G, spontaneous) (+ ∆G, nonspontaneous)

12. 6 Energy and Energy Conversions In principle, all reactions are reversible (A  B). Adding more A speeds up the forward reaction, A  B; adding more B speeds up the reverse reaction, B  A. At the point of chemical equilibrium, the relative concentrations of A and B are such that forward and reverse reactions take place at the same rate.

13. 6 ATP: Transferring Energy in Cells All living cells use adenosine triphosphate (ATP) for capture, transfer, and storage of energy. Some of the free energy released by certain exergonic (spontaneous) reactions is captured in ATP, which then can release free energy to drive endergonic (nonspontaneous) reactions.

14. Figure 6.5 ATP (Part 1)

15. 6 ATP: Transferring Energy in Cells ATP can hydrolyze to yield ADP and an inorganic phosphate ion (P i ). ATP + H 2 O  ADP + P i + free energy The reaction is exergonic (  G = –12 kcal/mol). Free energy of the P–O bond is much higher than the H–O bond that forms after hydrolysis. The formation of ATP from ADP and P i is endergonic and consumes as much free energy as is released by the breakdown of ATP: ADP + P i + free energy  ATP + H 2 O

16. Figure 6.6 The Energy-Coupling Cycle of ATP

17. Figure 6.7 Coupling ATP Hydrolysis to an Endergonic Reaction

18. 6 Enzymes: Biological Catalysts A catalyst is any substance that speeds up a chemical reaction without itself being used up. Living cells use biological catalysts to increase rates of chemical reactions. Most biological catalysts are proteins called enzymes. Certain RNA molecules called ribozymes are also catalysts.

19. 6 Enzymes: Biological Catalysts The direction of a reaction can be predicted if  G is known, but not the rate of the reaction. Some reactions are slow because there is an energy barrier between reactants and products. Exergonic reactions proceed only after the addition of a small amount of added energy, called the activation energy (E a ). Activation energy is the energy needed to put molecules into a transition state.

20. Figure 6.8 Activation Energy Initiates Reactions

21. 6 Enzymes: Biological Catalysts Enzymes solve this problem by lowering the energy barrier. Enzymes bind specific reactant molecules called substrates. Substrates bind to a particular site on the enzyme surface called the active site, where catalysis takes place. Enzymes are highly specific: They bind specific substrates and catalyze particular reactions under certain conditions. The specificity of an enzyme results from the exact three- dimensional shape and structure of the active site.

22. Figure 6.10 Enzyme and Substrate

23. 6 Enzymes: Biological Catalysts Binding a substrate to the active site produces an enzyme–substrate complex (ES). The enzyme–substrate complex (ES) generates the product (P) and free enzyme (E): E + S  ES  E + P

24. 6 Enzymes: Biological Catalysts Enzymes:  lower activation energy requirements  speed up the overall reaction  do not change the difference in free energy (  G) between the reactants and the products.

25. 6 Enzymes: Biological Catalysts Enzymes can have a profound effect on reaction rates. Reactions that might take years to happen can occur in a fraction of a second. At the active sites, enzymes and substrates interact by breaking old bonds and forming new ones.

26. 6 Enzymes: Biological Catalysts Enzymes catalyze reactions using one or more of the following mechanisms:  Orienting substrates  Inducing strain in substrates  Adding charges to substrates

27. 6 Enzymes: Biological Catalysts Hexokinase bound to glucose and glucose-6-phosphate Free program Cn3D from ( http://www.ncbi.nlm.nih.gov/Structure/) MMDB:8089

28. 6 Molecular Structure Determines Enzyme Function Most enzymes are much larger than their substrate. The active site of most enzymes is only a small region of the whole protein. The specificity of an enzyme for a particular substrate depends on a precise interlock = lock and key.

29. 6 Molecular Structure Determines Enzyme Function The change in enzyme shape caused by substrate binding is called induced fit. Induced fit at least partly explains why enzymes are so large. The rest of the macromolecule may have two functions:  To provide a framework so that the amino acids of the active site are properly positioned  To participate in the small changes in protein shape that allow induced fit

30. 6 Metabolism and the Regulation of Enzymes An organism’s metabolism is the total of all biochemical reactions taking place within it. Metabolism is organized into sequences of enzyme-catalyzed chemical reactions called pathways. In these sequences, the product of one reaction is the substrate for the next. A B C D enzyme

31. 6 Metabolism and the Regulation of Enzymes Some metabolic pathways are anabolic and synthesize the building blocks of macromolecules. Some are catabolic and break down macro- molecules and fuel molecules.

32. 6 Metabolism and the Regulation of Enzymes Enzyme activity can be inhibited by natural and artificial binders. Naturally occurring inhibitors regulate metabolism. Irreversible inhibition occurs when the inhibitor destroys the enzyme’s ability to interact with its normal substrate(s).

33. Figure 6.17 Irreversible Inhibition

34. 6 Metabolism and the Regulation of Enzymes Not all inhibition is irreversible. When an inhibitor binds reversibly to an enzyme’s active site, it competes with the substrate for the binding site and is called a competitive inhibitor.

35. Figure 6.18 (a) Reversible Inhibition (Part 1)

36. 6 Metabolism and the Regulation of Enzymes When an inhibitor binds reversibly to a site distinct from the active site, it is called a noncompetitive inhibitor. Noncompetitive inhibitors act by changing the shape of the enzyme in such a way that the active site no longer binds the substrate. Noncompetitive inhibitors can unbind from the enzyme, making the effects reversible.

37. Figure 6.18 (b) Reversible Inhibition (Part 1)

38. 6 Metabolism and the Regulation of Enzymes Metabolic pathways typically involve a starting material, intermediates, and an end product. Once the starting step occurs, other enzyme- catalyzed reactions follow until the product of the series builds up. One way to control the whole pathway is to have the end product inhibit the first step in the pathway. This is called end-product inhibition or feedback inhibition.

39. Figure 6.21 Inhibition of Metabolic Pathways